Adaptive evolution of pseudomonas aeruginosa during long-term co-culture with macrophages

Abstract

Adaptive evolution of bacterial pathogens to the host environment is critical for their success

during long-term infections. Previous studies have shown that adaptation of Pseudomonas

aeruginosa did occur during chronic infections, which is probably driven by physical

conditions, and the host immune system. Although various models have been developed to

gain insight into the evolution of bacterial pathogens in host environment, there is no current

model to study if the evolution of bacterial pathogens can be driven by phagocytes in vitro. In

this study, we co-cultured wildtype P. aeruginosa with macrophages for 28 days under

experimental conditions, and have identified two groups of mutants in replicate co-culture

populations, namely Autolytic lasR mutant, and mutants with rough colonies and enhanced

biofilm formation. The presence of both mutants in multiple co-culture populations suggested

parallel evolution of P. aeruginosa towards those two phenotypes. Our data demonstrated

that during in vitro co-culture, macrophages indeed drove the evolution of P. aeruginosa. In

agreement with clinical studies where both of the two mutants were found in Cystic Fibrosis

airways, our results also suggested that evolution of both mutants in vivo during chronic

infection might be driven by phagocytes from host immune system.